title: N-WASp is required for Schwann cell cytoskeletal dynamics, normal myelin gene expression and peripheral nerve myelination.
abstract: Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate the Schwann cell cytoskeleton are poorly defined. Here, we show that the actin cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated in myelinating Schwann cells coincident with myelin elaboration. When N-WASp is conditionally deleted in Schwann cells at the onset of myelination, the cells continue to ensheath axons but fail to extend processes circumferentially to elaborate myelin. Myelin-related gene expression is also severely reduced in the N-WASp-deficient cells and in vitro process and lamellipodia formation are disrupted. Although affected mice demonstrate obvious motor deficits these do not appear to progress, the mutant animals achieving normal body weights and living to advanced age. Our observations demonstrate that N-WASp plays an essential role in Schwann cell maturation and myelin formation.
authors.affiliation: Department of Haematology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fuzi
authors.initials: F
authors.lastname: Jin
authors.forename: Baoxia
authors.initials: B
authors.lastname: Dong
authors.forename: John
authors.initials: J
authors.lastname: Georgiou
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jinyi
authors.initials: J
authors.lastname: Zhang
authors.forename: Arjun
authors.initials: A
authors.lastname: Bharioke
authors.forename: Frank
authors.initials: F
authors.lastname: Qiu
authors.forename: Silvia
authors.initials: S
authors.lastname: Lommel
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.forename: Joel
authors.initials: J
authors.lastname: Eyer
authors.forename: Xiequn
authors.initials: X
authors.lastname: Chen
authors.forename: Alan C
authors.initials: AC
authors.lastname: Peterson
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005684:Gait / Q000235:genetics; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*
chemical_list: D051317:Wiskott-Aldrich Syndrome Protein, Neuronal